Selective alterations in CA1 spine morphology following dietary fructose intake.

Abstract

High fructose intake has been linked to metabolic and cognitive disturbances, yet its effects on hippocampal synaptic architecture remain unclear. We examined whether four weeks of fructose feeding alter metabolic parameters or CA1 synaptic ultrastructure in adult rats maintained on isocaloric AIN-93G diets containing fructose, glucose, or starch as the primary carbohydrate source. Serum biochemical and hormonal profiles showed only modest, diet-specific differences without major metabolic disruption. Quantitative electron microscopy revealed similar dendritic spine density, postsynaptic density length, perforated synapse frequency, and multisynaptic bouton density across groups, whereas fructose-fed rats displayed a small but significant reduction in spine area and an alteration in circularity. These localized geometric changes occurred without broader synaptic remodeling. Overall, our findings indicate that short-term fructose exposure under metabolically controlled, solid-diet conditions produces minimal metabolic and ultrastructural effects, in contrast to the pronounced disturbances reported in metabolically stressful paradigms, suggesting that structural consequences of fructose depend strongly on dietary context and metabolic load.